Aryl Carboxylic Acids Research Articles

Decarboxylative Cross-Coupling of Aryl Carboxylic Acids with Arylboronic Acids Using Ag/ZnO Catalyst under Aerobic Conditions in Aqueous Medium

Decarboxylative Cross-Coupling of Aryl Carboxylic Acids with Arylboronic Acids Using Ag/ZnO Catalyst under Aerobic Conditions in Aqueous Medium

Photo-induced carboxylation of C(sp2)−S bonds in aryl thiols and derivatives with CO2

Aryl thiols have proven to be a useful class of electron donors and hydrogen atom sources in photochemical processes. However, the direct activation and functionalization of C(sp2)–S bonds in aryl thiols remains elusive in the field of photochemistry. Herein, a photochemical carboxylation of C(sp2)–S bonds in aryl thiols with CO2 is reported, providing a synthetic route to important aryl carboxylic acids. Moreover, different kinds of aryl thiol derivatives, benzeneselenol and diphenyl diselenide also show moderate-to-high reactivity in this transformation. Mechanistic studies, including DFT calculations, suggest that the in situ generated carbon dioxide radical anion (CO2•−) and disulfide might be the key intermediates, which undergo radical substitution to yield products. This reaction features mild and catalyst-free conditions, good functional group tolerance and wide substrate scope. Furthermore, the efficient degradation of polyphenylene sulfide highlights the usefulness of this methodology.

Transition-metal-free and solvent-tolerant decarboxylative iodination of aromatic carboxylic acids

Current decarboxylative halogenation methods typically require expensive or toxic transition metal catalysts and have limited solvent compatibility. Herein, we report a novel transition-metal-free and solvent-tolerant decarboxylative iodination method by using iodine monochloride in the presence of potassium phosphate, which are effective to readily available aryl and heteroaryl carboxylic acids, and can be executed in a variety of solvents, including water.

Copper‐Mediated Decarboxylative Trifluoromethylselenolation of Alkynyl Carboxylic Acids with [Me4N][SeCF3

AbstractThe synthesis of alkynyl trifluoromethyl selenoethers from copper‐mediated aerobic decarboxylative trifluoromethylselenolation of alkynyl carboxylic acids with [Me4N][SeCF3] is reported. The reaction proceeded smoothly under mild conditions and enabled the facile conversion of both aryl and alkyl alkynyl carboxylic acids to the corresponding trifluoromethyl selenoethers in good yields, demonstrating that decarboxylative trifluoromethylselenolation of alkynyl carboxylic acids with the nucleophilic [Me4N][SeCF3] reagent is feasible at ambient temperature without irradiation. Advantages of the method include the use of bench‐stable and non‐volatile alkynyl carboxylic acids as starting materials, readily accessible SeCF3 reagent, excellent functional group tolerance, and the avoidance of harsh reaction conditions. This copper‐mediated reaction represents the first decarboxylative trifluoromethylselenolation of alkynyl carboxylic acids with a SeCF3 source.

High-Fidelity Supramolecular Chirality Transportation Enabled Through Chalcogen Bonding.

The formation of asymmetric microenvironments in proteins benefits from precise transportation of chirality across multiple levels through weak bonds in the folding and assembly process, which inspires the rational design and fabrication of artificial chiral materials. Herein, the chalcogen bonding-directed precise transportation of supramolecular chirality toward multiple levels is reported to aid the fabrication of chiroptical materials. Benzochalcogenadiazole (O, S, Se) motifs are conjugated to amino acid residues, and the solid-state assemblies afforded selective supramolecular chirality with handedness depending on the kinds of chalcogen atoms and amino acids. The chalcogen-N sequence assisted by hydrogen bonding synergistically allows for the complexation with pyrene conjugated aryl carboxylic acids to give macroscopic helical structures with active circular dichroism and circularly polarized luminescence, of which handedness is precisely determined by the pristine chiral species. Then the further application of chiral benzochalcogenadiazole motifs as seeds in directing handedness of benzamide via symmetry breaking is realized. Behaving as the dopants, embedding into the matrix of benzophenone induces the room temperature phosphorescence, whereby the thermal chiroptical switch is fabricated with color-tunable phosphorescent circularly polarized luminescence. This work utilized benzochalcogenadiazole-based chiral building units to accomplish precise transportation of supramolecular chirality in coassemblies with high-fidelity, achieving flexible manipulation of chiroptical properties and macroscopic helical sense.

Photoinduced Ligand-to-Copper Charge Transfer for Aryl Decarboxylative Allylation, Thiolation, and Bromination.

Herein, aryl decarboxylative allylation, thiolation, and bromination reactions via photoinduced ligand-to-copper charge transfer are described. Utilizing inexpensive copper metal, the transformations of various aryl carboxylic acids enable the rapid synthesis of the corresponding alkene, thioether, and aryl bromide derivatives under visible light irradiation, which offers significant synthetic value. The reaction conditions are mild and straightforward, exhibiting a broad substrate compatibility. Furthermore, this method can be applied for the late-stage modification of complex drug molecules.

Photochemical Synthesis of Thioesters from Aryl Halides and Carboxylic Acids

Photochemical Synthesis of Thioesters from Aryl Halides and Carboxylic Acids

Photocatalysed eosin Y mediated synthesis of biologically potent 4 (3H)-quinazolinone

An environmentally benign green and metal-free visible light mediated approach for the synthesis of biologically potent 4(3H)-quinazolinone through multicomponent reaction of readily available starting materials potassium salt of anthranilic acid, aryl carboxylic acid, aliphatic/aromatic amine catalyzed by Eosin-Y has been developed with wide range of applications in pharmaceutical. Integrated process reduces the mechanical loss of the intermediate during the process of isolation.

Photosensitized Reductive Elimination of Gold(III) to Enable Esterification of Aryl Iodides with Carboxylic Acids.

Compared to the well-established transition metal-catalyzed cross-coupling reactions, Au(I)/Au(III)-catalyzed cross-coupling reactions have lagged behind. Despite some advancements, achieving gold-catalyzed C-O coupling with carboxylic acids via an Au(III) carboxylate intermediate remains challenging due to the thermal unfavorability of the critical reductive elimination step. Here, we present the first photosensitized reductive elimination of gold(III) to enable esterification of aryl iodides with carboxylic acids. In the presence of a (P, N)-gold(I) catalyst and a photosensitizer benzophenone under blue LED irradiation, esterification derivatives were obtained from aryl iodides with both aryl and alkyl (1°, 2°, 3°) carboxylic acids. Mechanistic and modeling studies support that energy transfer (EnT) from a photosensitizer produces an excited-state gold(III) complex that couples aryl iodides with carboxylic acids. This photoinduced energy-transfer strategy has been applied in several other photosensitized gold catalysis reactions, indicating its potential for further applications.

Photochemical Synthesis of Thioesters from Aryl Halides and Carboxylic Acids

AbstractThioesters are important in synthesis, materials science, and biology, and their preparation traditionally relies on the use of disagreeable thiols. Here, we report a thiol‐free protocol that stitches together widespread carboxylic acids and aryl halides, producing a diverse array of thioesters. Crucial to this strategy is the discovery that tetramethylthiourea can serve as both a sulfur source and, upon direct excitation by purple light, as a strong reductant, suitable for activating aryl halides via single‐electron transfer. Coupling of the resulting aryl radicals provides an isothiouronium ion intermediate, which can be attacked by carboxylic acids via a polar pathway, affording the thioester products under mild conditions.

Photochemical Synthesis of Thioesters from Aryl Halides and Carboxylic Acids.

Thioesters are important in synthesis, materials science, and biology, and their preparation traditionally relies on the use of disagreeable thiols. Here, we report a thiol-free protocol that stitches together widespread carboxylic acids and aryl halides, producing a diverse array of thioesters. Crucial to this strategy is the discovery that tetramethylthiourea can serve as both a sulfur source and, upon direct excitation by purple light, as a strong reductant, suitable for activating aryl halides via single-electron transfer. Coupling of the resulting aryl radicals provides an isothiouronium ion intermediate, which can be attacked by carboxylic acids via a polar pathway, affording the thioester products under mild conditions.

Photoinduced Cu(II)‐Mediated Decarboxylative Thianthrenation of Aryl and Heteroaryl Carboxylic Acids

Given that (hetero)aryl carboxylic acids are inexpensive materials available in a great variety from commercial and natural resources or synthesis, the strategies enabling their use as starting materials for preparing fine chemicals are highly sought after. Here we report a photoinduced Cu(II)‐mediated protocol converting (hetero)aryl carboxylic acids into (hetero)aryl thianthrenium salts, high value‐added building blocks that can undergo various subsequent transformations, creating an attractive two‐step pathway for the divergent functionalization of these ubiquitous starting materials. The excellent compatibility of the method is shown by preparing a broad range of sterically and electronically varied (hetero)aryl thianthrenium salts, including derivatives of pharmaceuticals, such as ataluren, celecoxib, flavoxate, probenecid, repaglinide, and tamibarotene. The syntheses of 13C‐labeled probenecid and bioisosteres of ataluren as well as the unconventional modifications of celecoxib and flavoxate, illustrate the synthetic potential of the strategy. Mechanistic studies are in line with a reaction occurring through a photoinduced ligand‐to‐metal charge transfer (LMCT) of Cu(II)‐arylcarboxylates, enabling radical decarboxylative carbometallation to form arylcopper(II) intermediates that in turn react with thianthrene to form the product. Noteworthy, the susceptibility of aryl thianthrenium salts to photodegradation is overcome by a Cu(I)‐driven salvage loop, which continuously intercepts the transiently formed radicals and regenerates the products.

Photoinduced Cu(II)-Mediated Decarboxylative Thianthrenation of Aryl and Heteroaryl Carboxylic Acids.

Given that (hetero)aryl carboxylic acids are inexpensive materials available in a great variety from commercial and natural resources or synthesis, the strategies enabling their use as starting materials for preparing fine chemicals are highly sought after. Here we report a photoinduced Cu(II)-mediated protocol converting (hetero)aryl carboxylic acids into (hetero)aryl thianthrenium salts, high value-added building blocks that can undergo various subsequent transformations, creating an attractive two-step pathway for the divergent functionalization of these ubiquitous starting materials. The excellent compatibility of the method is shown by preparing a broad range of sterically and electronically varied (hetero)aryl thianthrenium salts, including derivatives of pharmaceuticals, such as ataluren, celecoxib, flavoxate, probenecid, repaglinide, and tamibarotene. The syntheses of 13 C-labeled probenecid and bioisosteres of ataluren as well as the unconventional modifications of celecoxib and flavoxate, illustrate the synthetic potential of the strategy. Mechanistic studies are in line with a reaction occurring through a photoinduced ligand-to-metal charge transfer (LMCT) of Cu(II)-arylcarboxylates, enabling radical decarboxylative carbometallation to form arylcopper(II) intermediates that in turn react with thianthrene to form the product. Noteworthy, the susceptibility of aryl thianthrenium salts to photodegradation is overcome by a Cu(I)-driven salvage loop, which continuously intercepts the transiently formed radicals and regenerates the products.

Graphitisches Kohlenstoffnitrid als Photokatalysator für die decarboxylative C(sp2)−C(sp3) Kupplung mittels Nickelkatalyse

AbstractDie Entwicklung robuster und zuverlässiger Methoden für den Aufbau von C(sp2)−C(sp3)‐Bindungen ist entscheidend, um eine Vielzahl strukturell diverser Substanzen in der Wirkstoffforschung und ‐entwicklung zugänglich zu machen. Obwohl bedeutende Fortschritte auf diesem Gebiet durch den Einsatz der Metallaphotoredox‐Chemie erzielt wurden, nutzen viele dieser Methoden nach wie vor Photokatalysatoren auf Edelmetallbasis aufgrund ihrer effizienten Redoxprozesse und gut anpassbaren Eigenschaften. Aufgrund der hohen Kosten, Ressourcenknappheit und oftmals erheblichen Toxizität dieser Metalle, ist es von großem Interesse, die Suche nach geeigneten Ersatz voranzutreiben. In dieser Publikation zeigen wir den Einsatz des kommerziell erhältlichen, heterogenen Halbleiters graphitisches Kohlenstoffnitrid (gCN) als Photokatalysator in Kombination mit Nickelkatalyse für die Kreuzkupplung von Arylhalogenid‐ und Carbonsäure‐Derivaten. Wie in vorherigen Berichten gezeigt, kann gCN effektiv an Einelektronenübertragungen (SET) und Energietransfer‐(EnT) Prozessen zur Bildung von C−X‐Bindungen teilnehmen. Dieses Manuskript beinhaltet neue Strategien, um die bislang auf C−O Bindungsknüpfung beschränkten Methoden mittels carbonsäurehaltigen Bausteinen um C−C Bindungsknüpfungen zu erweitern. Es wird gezeigt, dass eine Vielzahl an Arylhalogeniden als auch Carbonsäuren für diese Transformation genutzt werden kann. Im Weiteren wird das Recycling des Photokatalysators demonstriert und der Mechanismus der Reaktion untersucht.

Graphitic Carbon Nitride as a Photocatalyst for Decarboxylative C(sp2)-C(sp3) Couplings via Nickel Catalysis.

The development of robust and reliable methods for the construction of C(sp2)-C(sp3) bonds is vital for accessing an increased array of structurally diverse scaffolds in drug discovery and development campaigns. While significant advances towards this goal have been achieved using metallaphotoredox chemistry, many of these methods utilise photocatalysts based on precious-metals due to their efficient redox processes and tuneable properties. However, due to the cost, scarcity, and toxicity of these metals, the search for suitable replacements should be a priority. Here, we show the use of commercially available heterogeneous semiconductor graphitic carbon nitride (gCN) as a photocatalyst, combined with nickel catalysis, for the cross-coupling between aryl halide and carboxylic acid coupling partners. gCN has been shown to engage in single-electron-transfer (SET) and energy-transfer (EnT) processes for the formation of C-X bonds, and in this manuscript we overcome previous limitations to furnish C-C over C-O bonds using carboxylic acids. A broad scope of both aryl halides and carboxylic acids is presented, and recycling of the photocatalyst demonstrated. The mechanism of the reaction is also investigated.

Selective N-functionalization of Arylhydrazines with Primary Alcohols and Acids under PPh3/DDQ System.

We present a PPh3/DDQ-mediated regiospecific selective N-functionalization of arylhydrazines with primary benzylic alcohols and aryl carboxylic acids for the synthesis of N1-benzyl arylhydrazines and N2-acyl arylhydrazines, respectively. This metal- and base-free approach features very short reaction times (about 10 min), broad substrate scope, good functional group tolerance, and mild reaction conditions. Furthermore, N1-benzlated products have also been successfully applied to the concise synthesis of N-substituted indoles and anticancer drug MDM2 inhibitor.

Design, Synthesis, and Biological Evaluation of 1,2,4-Oxadiazole Derivatives Containing an Aryl Carboxylic Acid Moiety as Potent Sarbecovirus Papain-like Protease Inhibitors.

Papain-like protease (PLpro) is a promising therapeutic target for its pivotal role in the life cycle of SARS-CoV-2. A series of 1,2,4-oxadiazole derivatives was designed and synthesized via a ring formation strategy based on SARS-CoV-2 PLpro-GRL0617 complex structure. Systematic structure-activity relationship studies revealed that introducing oxadiazole and aryl carboxylic acid moieties to GRL0617 enhanced the enzymatic inhibition activity, affinity, and deubiquitination capacity toward PLpro. 1,2,4-Oxadiazole compounds 13f and 26r, which had PLpro inhibition activity (IC50 = 1.8 and 1.0 μM) and antiviral activity against SARS-CoV-2 (EC50 = 5.4 and 4.3 μM), exhibited good metabolic stability (t1/2 > 93.2 min) and higher plasma exposure (AUC0-t = 17,380.08 and 24,289.76 ng·h/mL) in mice. Especially, compound 26r with moderate oral bioavailability of 39.1% and potent antiviral activity is worthy of further studies in vivo. Our findings provide a new insight for the discovery of antiviral agents targeting PLpro.

Solar Carboxylation Using CO2: Interfacially Synthesized Flexible Covalent Organic Frameworks Film as a Photocatalyst for Highly Selective Solar Carboxylation of Arylamines with CO2.

Carbon dioxide (CO2) conversion into value-added chemicals/fuels by utilizing solar energy is a sustainable way to mitigate our dependence on fossil fuels and stimulate a carbon-neutral economy. However, the efficient and affordable conversion of CO2 is still an ongoing challenge. Here, we report an interfacially synthesized visible-light-active Ni(II)-integrated covalent organic frameworks (TaTpBpy-Ni COFs) film as a photocatalyst for efficient CO2 conversion into carboxylic acid under ambient conditions. Notably, the TaTpBpy-Ni COFs film showed excellent photocatalytic activity for the carboxylation of various arylamines with CO2 to the corresponding arylcarboxylic acid via C-N bond activation under solar-light irradiation. Moreover, this carboxylation protocol exhibits mild reaction conditions and good functional group tolerance without the necessity of using stoichiometric metallic reductants. This work shows a benchmark example of not only the interfacially synthesized COFs film used as a photocatalyst for solar-light energy utilization but also the selective solar chemical production system of arylcarboxylic acid directly from CO2.

Direct esterification of amides by the dimethylsulfate-mediated activation of amide C–N bonds

Amides are important intermediates in organic chemistry and the pharmaceutical industry, but their low reactivity requires catalysts and/or severe reaction conditions for esterification. Here, a novel approach was devised to convert amides into esters without the use of transition metals. The method effectively overcomes the inherent low reactivity of amides by employing dimethylsulfate-mediated reaction to activate the C-N bonds. To confirm the proposed reaction mechanism, control experiments and density functional theory (DFT) calculations were conducted. The method demonstrates a wide array of substrates, including amides with typical H/alkyl/aryl substitutions, N,N-disubstituted amides, amides derived from alkyl, aryl, or vinyl carboxylic acids, and even amino acid substrates with stereocentres. Furthermore, we have shown the effectiveness of dimethylsulfate in removing acyl protective groups in amino derivatives. This study presents a method that offers efficiency and cost-effectiveness in broadening the esterification capabilities of amides, thereby facilitating their increased utilization as synthetic compounds in diverse transformations.

General Approach to Amides through Decarboxylative Radical Cross-Coupling of Carboxylic Acids and Isocyanides.

Herein, we report a silver-catalyzed protocol for decarboxylative cross-coupling between carboxylic acids and isocyanides, leading to linear amide products through a free-radical mechanism. The disclosed approach provides a general entry to a variety of decorated amides, accommodating a diverse array of radical precursors, including aryl, heteroaryl, alkynyl, alkenyl, and alkyl carboxylic acids. Notably, the protocol proved to be efficient for decarboxylative late-stage functionalization of several elaborate pharmaceuticals, demonstrating its potential applications.